Serotonin (5-hydroxytryptamine; 5-HT) mediates many central and peripheral nervous functions by its interaction with specific neuronal receptors. The 5-HT receptors are implicated in various normal physiological responses, e.g., smooth muscle contraction, platelet aggregation, aldosterone production, circadian rhythm, and neuronal development and various disorders such as migraine headaches, anxiety, mental depression, and undesired behavior. 5-HT receptors are also binding sites for hallucinogenic drugs. At least sixteen serotonin receptors belonging to seven subtypes have been identified. A better understanding of the localization (the sites of action) and regulation of 5-HT receptors may lead to development of receptor specific drugs. Through SBIR Phase I funding, we have developed monoclonal antibodies that are highly specific to the three members of the 5-HT2 receptor family. As a continuation of this project, we proposed to generate monoclonal antibodies to the rest of the 5-HT receptors. Antibodies will be screened for their utility in immunohistochemistry, western blot, and immunoprecipitation. We also propose to develop molecular probes for detection and quantitation of 5-HT receptors by PCR and RNase protection assay. The combination of monoclonal antibodies and the probes for PCR and RNase protection assay will provide powerful research tools for fundamental and applied serotonin receptor research. PROPOSED COMMERCIAL APPLICATIONS: The result of this study will provide tools, which can be readily commercialized as research reagents. At present monoclonal antibodies to 5-HTRs (other than to 5-HT2 receptor developed by us) and RNase protection assay probes are not available. Since the field of serotonin research field is large and more than 27,000 articles with potential significance for clinical application have been published in the last ten years, we predict the market to be of a reasonable size.